Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

Interfering with bacterial cell-to-cell communication is a promising strategy to combat antimicrobial resistance. The natural product hamamelitannin and several of its analogues have been identified as quorum sensing inhibitors. In this paper the synthesis of pyrrolidine-based analogues of a more lead-like hamamelitannin analogue is reported. A convergent synthetic route based on a key ring-closing metathesis reaction was developed and delivered the pyrrolidine analogue in 17 steps in high yield. Chemoselective derivatization of the pyrrolidine nitrogen atom resulted in 6 more compounds. The synthesized compounds were evaluated in a biofilm model, but were all inactive

On the Road – My life as a Theater Creator

The text presents a trajectory of the actress, director and Israeli singer Yael Rasooly.Keywords: Theater of animation. Yael Rasooly. Creation process

Competitive equilibrium and the double auction

In this paper, we revisit the common claim that double auctions necessarily generate competitive equilibria. We begin by observing that competitive equilibrium has some counterintuitive implications: specifically, it predicts that monotone shifts in the value distribution can leave prices unchanged. Using experiments, we then test whether these implications are borne out by the data. We find that in double auctions with stationary value distributions, the resulting prices can be far from competitive equilibria. We also show that the effectiveness of our counterexamples is blunted when traders can leave without replacement as time progresses. Taken together, these findings suggest that the `Marshallian path' is crucial for generating equilibrium prices in double auctions

Na Estrada – minha vida como criadora teatral

O texto apresenta a trajetória da atriz, diretora e cantora israelense Yael Rasooly. A artista reflete sobre a sua formação artística, evidenciando o papel desempenhado pela família; pela Escola de Teatro Visual de Jerusalém; pela música erudita e música pop; pelo cinema e por diretores teatrais. Analisa o seu processo e criação, a opção por trabalhar como solista, e o desafio de interpretar diversas personagens no mesmo espetáculo. Num tom ao mesmo tempo analítico e confessional, o texto possibilita conhecer as opções profissionais e artísticas da autora.Palavras-chave: Teatro de animação. Yael Rasooly. Processo de criação

Achieving maternal and child health gains in Afghanistan: a Countdown to 2015 country case study.

BACKGROUND: After the fall of the Taliban in 2001, Afghanistan experienced a tumultuous period of democracy overshadowed by conflict, widespread insurgency, and an inflow of development assistance. Although there have been several cross-sectional assessments of health gains over the last decade, there has been no systematic analysis of progress and factors influencing maternal and child health in Afghanistan. METHODS: We undertook a comprehensive, systematic assessment of reproductive, maternal, newborn, and child health in Afghanistan over the last decade. Given the paucity of high-quality data before 2001, we relied mainly on 11 nationally representative surveys conducted between 2003 and 2013. We estimated national and subnational time trends for key reproductive, maternal, and child health indicators, and used linear regression methods to determine predictors of change in health-care service use. All analyses were weighted for sampling and design effects. Additional information was collated and analysed about health system performance from third party surveys and about human resources from the Afghan Ministry of Public Health. FINDINGS: Between 2003 and 2015, Afghanistan experienced a 29% decline in mortality of children younger than 5 years. Although definite reductions in maternal mortality remain uncertain, concurrent improvements in essential maternal health interventions suggest parallel survival gains in mothers. In a little over a decade (2003-13 inclusive), coverage of several maternal care interventions increased-eg, for antenatal care (16% to 53%), skilled birth attendance (14% to 46%), and births in a health facility (13% to 39%). Childhood vaccination coverage rates for the basic vaccines from the Expanded Programme of Immunisation (eg, BCG, measles, diphtheria-tetanus-pertussis, and three doses of polio) doubled over this period (about 40% to about 80%). Between 2005 and 2013, the number of deployed facility and community-based health-care professionals also increased, including for nurses (738 to 5766), midwives (211 to 3333), general physicians (403 to 5990), and community health workers (2682 to 28 837). Multivariable analysis of factors contributing to overall changes in skilled birth attendance and facility births suggests independent contributions of maternal literacy, deployment of community midwives, and proximity to a facility. INTERPRETATION: Despite conflict and poverty, Afghanistan has made reasonable progress in its reproductive, maternal, newborn, and child health indicators over the last decade based on contributions of factors within and outside the health sector. However, equitable access to health care remains a challenge and present delivery models have high transactional costs, affecting sustainability. To maintain and further accelerate health and development gains, future strategies in Afghanistan will need to focus on investments in improving social determinants of health and targeted cost-effective interventions to address major causes of maternal and newborn mortality. FUNDING: US Fund for UNICEF under the Countdown to 2015 for Maternal, Newborn, and Child Survival grant from the Bill & Melinda Gates Foundation, and from the Government of Canada, Foreign Affairs, Trade and Development Canada. Additional direct and in-kind support was received from the UNICEF Country Office Afghanistan, the Centre for Global Child Health, the Hospital for Sick Children, Toronto, the Aga Khan University, and Mother and Child Care Trust (Pakistan)

Scale-up protein separation on stainless steel wide bore toroidal columns in the type-J counter-current chromatography

Manufacturing high-value added biotech biopharmaceutical products (e.g. therapeutic proteins) requires quick-to-develop, GMP-compliant, easy-to-scale and cost effective preparatory chromatography technologies. In this work, we describe the construction and testing of a set of 5-mm inner diameter stainless steel toroidal columns for use on commercially available preparatory scale synchronous J-type counter-current chromatography (CCC) machinery. We used a 20.2 m long column with an aqueous two-phase system containing 14% (w/w) PEG1000 and 14% (w/w) potassium phosphate at pH 7, and tested a sample loading of 5% column volume and a mobile phase flow rate of 20 ml/min. We then satisfactorily demonstrated the potential for a weekly protein separation and preparation throughput of ca. 11 g based on a normal weekly routine for separating a pair of model proteins by making five stacked injections on a single portion of stationary phase with no stripping. Compared to our previous 1.6 mm bore PTFE toroidal column, the present columns enlarged the nominal column processing throughput by nearly 10. For an ideal model protein injection modality, we observed a scaling up factor of at least 21. The 2 scales of protein separation and purification steps were realized on the same commercial CCC device.The BBSRC Grant number BB/FOF/206. YHG and YZ also acknowledge financial support by National Basic Research Program (973 Program 2013CB733600).Ms Yan Zhao (School of Mechanical and Power Engineering) has been grateful to a Training Program of Innovation and Entrepreneurship for Undergraduates Grant number X13219 by East China University of Science and Technology. Contribution and/or encouragement to this work from D. Fisher, T. Bunce, Ying-Dong Liu, Zheng-Tao Zhang, Li-Li Ba

A look at the orthographic challenges of Afghanistan's Uzbek language

The Uzbek language belongs to the eastern branch of Turkic languages. Turkic languages are part of the Ural-Altaic language family. The history of orthography and ancient literature of the Uzbek language goes back to the 'Orkhon Yinisey' stone in orthography ions. These petroglyphs were obtained from the beach of the Orkhon Seas in Mangolia, Yenisey (Anasay-Mother valley) in southern Siberia, Talas in Kyrgyzstan, and other areas such as Eastern Turkistan, Central Asia, Caucasus, Volga beach and parts of Europe area. These historical sites contain Turkish-Ronics writings. In the stone in orthography ions of 'Orkhon Yinisey', some of which include eulogies and hymns describing Turkish kings, are carved on the tombstones of Turkish kings and princes. The orthography of the Uzbek language of Uzbekistan has always changed from the previous state. However, the Uzbek orthography in Afghanistan has never changed since the 12th century until now; they use the Arabic-Uzbek orthography. In this research, library resources are used

Policies to improve end-of-life decisions in Flemish hospitals: communication, training of health care providers and use of quality assessments

<p>Abstract</p> <p>Background</p> <p>The prevalence and implementation of institutional end-of-life policies has been comprehensively studied in Flanders, Belgium, a country where euthanasia was legalised in 2002. Developing end-of-life policies in hospitals is a first step towards improving the quality of medical decision-making at the end-of-life. Implementation of policies through quality assessments, communication and the training and education of health care providers is equally important in improving actual end-of-life practice. The aim of the present study is to report on the existence and nature of end-of-life policy implementation activities in Flemish acute hospitals.</p> <p>Methods</p> <p>A cross-sectional mail survey was sent to all acute hospitals (67 main campuses) in Flanders (Belgium). The questionnaire asked about hospital characteristics, the prevalence of policies on five types of end-of-life decisions: euthanasia, palliative sedation, alleviation of symptoms with possible life-shortening effect, do-not-resuscitate decision, and withdrawing or withholding of treatment, the internal and external communication of these policies, training and education on aspects of end-of-life care, and quality assessments of end-of-life care on patient and family level.</p> <p>Results</p> <p>The response rate was 55%. Results show that in 2007 written policies on most types of end-of-life decisions were widespread in acute hospitals (euthanasia: 97%, do-not-resuscitate decisions: 98%, palliative sedation: 79%). While standard communication of these policies to health care providers was between 71% and 91%, it was much lower to patients and/or family (between 17% and 50%). More than 60% of institutions trained and educated their caregivers in different aspects on end-of-life care. Assessment of the quality of these different aspects at patient and family level occurred in 25% to 61% of these hospitals.</p> <p>Conclusions</p> <p>Most Flemish acute hospitals have developed a policy on end-of-life practices. However, communication, training and the education of health care providers about these policies is not always provided, and quality assessment tools are used in less than half of the hospitals.</p